Luellmann, Color Atlas of Pharmacology 2005 Thieme Inhibition of DNA and RNA synthesis (A).
Inhibition of nucleobase synthesis (2). Tet-
Mitosis is preceded by replication of chro- rahydrofolic acid (THF) is required for the synthesis of both purine bases and thymi- protein synthesis (RNA synthesis). Existing dine. Formation of THF from folic acid in- DNA (gray) serves as a template for the syn- volves dihydrofolate reductase (p. 274). The folate analogues aminopterin and methotrex- synthesis may be inhibited by the following ate (amethopterin) inhibit enzyme activity.
Cellular stores of THF are depleted. The effectof these antimetabolites can be reversed by Damage to the template (1). Alkylating cy-
administration of folinic acid (5-formyl-THF, tostatics are reactive compounds that trans-
leucovorin, citrovorum factor). Hydroxyurea fer alkyl residues into a covalent bond with (hydroxycarbamide) inhibits ribonucleotide DNA. For instance, mechlorethamine (nitro- gen mustard) is able to cross-link double- cleotides into deoxyribonucleotides subse- quently used as DNA building blocks.
atoms. Correct reading of genetic informa-tion is thereby rendered impossible. Other Incorporation of false building blocks (3).
alkylating agents are chlorambucil, mel- Unnatural nucleobases (6-mercaptopurine; phalan, thio-TEPA, cyclophosphamide, ifos- 5-fluorouracil) or nucleosides with incorrect famide, lomustine, and busulfan. Specific sugars (cytarabine) act as antimetabolites.
adverse reactions include irreversible pul- They inhibit DNA/RNA synthesis or lead to monary fibrosis due to busulfan and hemor- synthesis of missense nucleic acids.
rhagic cystitis caused by the cyclophospha- formation of the inactive precursor azathio- prine (p. 37). The uricostatic allopurinol captoethanesulfonate). The platinum-con-
(p. 327) inhibits the degradation of 6-mer- taining compounds cisplatin and carbopla-
captopurine such that coadministration of tin release platinum, which binds to DNA.
Cystostatic antibiotics insert themselves
into the DNA double strand; this may lead tostrand breakage (e. g., with bleomycin). The Combination therapy. Cytostatics are fre-
anthracycline antibiotics daunorubicin and quently administered in complex therapeu- adriamycin (doxorubicin) may induce cardio- Induction of strand breakage may result
Supportive therapy. Cancer chemotherapy
from inhibition of topoisomerase. The epi-
can be supported by adjunctive medications.
podophyllotoxins etoposide and tenoposide
Thus, 5-HT3 serotonin receptor antagonists interact with topoisomerase II, which func- (e. g., ondansetron, p. 342) afford effective tions to split, transpose, and reseal DNA strands (p. 276); these agents cause strand highly emetogenic drugs such as cisplatin.
breakage by inhibiting resealing. The “te- cans” topotecan and irinotecan are deriva- acted by granulocyte and granulocyte/mac- tives of camptothecin from the fruits of a rophage colony-stimulating factors (filgras- Chinese tree (Camptotheca acuminata). They tim and lenograstim and molgramostim, re- Luellmann, Color Atlas of Pharmacology 2005 ThiemeAll rights reserved. Usage subject to terms and conditions of license. Luellmann, Color Atlas of Pharmacology 2005 Thieme A. Cytostatics: alkylating agents and cytostatic antibiotics (1),
inhibitors of tetrahydrofolate synthesis (2), antimetabolites (3)
to template
Inhibition of nucleotide synthesis
Insertion of incorrect building blocks
Luellmann, Color Atlas of Pharmacology 2005 ThiemeAll rights reserved. Usage subject to terms and conditions of license.
  • The Aims of Isolating Active Principles
  • European Plants as Sources of Effective Medicines
  • Congeneric Drugs and Name Diversity
  • Drug Administration by Inhalation
  • From Application to Distribution in the Body
  • Potential Targets of Drug Action
  • Possible Modes of Drug Distribution
  • Biotransformation of Drugs cont.
  • Drug Metabolism by Cytochrome P450
  • The Kidney as an Excretory Organ
  • Drug Concentration in the Body as a Function of Time— First Order ( Exponential) Rate Processes
  • Time Course of Drug Concentration in Plasma
  • Time Course of Drug Plasma Levels during Repeated Dosing ( A)
  • Time Course of Drug Plasma Levels during Irregular Intake ( B)
  • Accumulation: Dose, Dose Interval, and Plasma Level Fluctuation ( A)
  • Change in Elimination Characteristics during Drug Therapy ( B)
  • Concentration–Effect Relationship ( A)
  • Concentration–Effect Curves (B)
  • Models of the Molecular Mechanism of Agonist/ Antagonist Action ( A)
  • Enantioselectivity of Drug Action
  • Mode of Operation of G-Protein-coupled Receptors
  • Time Course of Plasma Concentration and Effect
  • Undesirable Drug Effects, Side Effects
  • Drug Toxicity in Pregnancy and Lactation
  • Drugs Acting on the Sympathetic Nervous System
  • Structure of the Sympathetic Nervous System
  • Adrenoceptor Subtypes and Catecholamine Actions
  • Structure–Activity Relationships of Sympathomimetics
  • Alpha-Sympathomimetics, Alpha-Sympatholytics
  • Beta-Sympatholytics (Beta-Blockers)
  • Drugs Acting on the Parasympathetic Nervous System
  • Localization of Nicotinic ACh Receptors
  • Effects of Nicotine on Body Function
  • Histamine Effects and Their Pharmacological Properties
  • Drugs Used to Influence Smooth Muscle Organs
  • Electrophysiological Actions of Antiarrhythmics of the Na+- Channel Blocking Type
  • Drugs for the Treatment of Anemias
  • Prophylaxis and Therapy of Thromboses
  • Vitamin K Antagonists and Vitamin K
  • Possibilities for Interference (B)
  • Intra-arterial Thrombus Formation ( A)
  • Formation, Activation, and Aggregation of Platelets ( B)
  • Inhibitors of Platelet Aggregation ( A)
  • NaCl Reabsorption in the Kidney (A)
  • Diuretics of the Sulfonamide Type
  • Drugs for the Treatment of Peptic Ulcers
  • Drugs for Gastric and Duodenal Ulcers
  • Drugs for Gastric and Duodenal Ulcers cont.
  • Nondepolarizing Muscle Relaxants
  • Nonsteroidal Anti-inflammatory Drugs ( NSAIDs)
  • Opioid Analgesics-Morphine Type cont. 1
  • Opioid Analgesics-Morphine Type cont. 2
  • General Anesthesia and General Anesthetic Drugs
  • Pharmacokinetics of Benzodiazepines
  • Therapy of Depressive Illness cont.
  • Psychotomimetics (Psychedelics, Hallucinogens)
  • Hypothalamic and Hypophyseal Hormones
  • Hyperthyroidism and Antithyroid Drugs
  • Androgens, Anabolic Steroids, Antiandrogens
  • Follicular Growth and Ovulation, Estrogen and Progestin Production
  • Antiestrogen and Antiprogestin Active Principles
  • Treatment of Insulin-dependent Diabetes Mellitus
  • Treatment of Maturity-Onset (Type II) Diabetes Mellitus
  • Drugs for Maintaining Calcium Homeostasis
  • Drugs for Treating Bacterial Infections
  • Inhibitors of Cell Wall Synthesis
  • Inhibitors of Cell Wall Synthesis cont.
  • Inhibitors of Tetrahydrofolate Synthesis
  • Inhibitors of Protein Synthesis cont.
  • Drugs for Treating Mycobacterial Infections
  • Drugs Used in the Treatment of Fungal Infections
  • Chemotherapy of Viral Infections
  • Chemotherapy of Viral Infections cont.
  • Drugs for Treating Endoparasitic and Ectoparasitic Infestations
  • Chemotherapy of Malignant Tumors
  • Targeting of Antineoplastic Drug Action ( A)
  • Mechanisms of Resistance to Cytostatics ( B)
  • Inhibition of Immune Responses cont.
  • Antidotes and Treatment of Poisonings
  • Antidotes and Treatment of Poisonings cont.
  • Acute Coronary Syndrome—Myocardial Infarction
  • Obesity—Sequelae and Therapeutic Approaches
  • Source: http://khotanbooks.org/UploadedFiles/PFiles/8c4aac280af04fe.pdf


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